Paramethadione

Concurrent use of alcohol or CNS depression-producing medications with dione anticonvulsants may enhance CNS depression. /Dione anticonvulsants/

Concurrent use of tricyclic antidepressants; haloperidol; loxapine; maprotiline; molindone; monoamine oxidase (MAO) inhibitors, including furazolidone, procarbazine, and >10 mg/day selegiline; phenothiazines; pimozide; or thioxanthenes with dione anticonvulsants may lower the convulsive threshold, enhance CNS depression, and decrease the effects of the anticonvulsant medication. dosage adjustments may be necessary. /Dione anticonvulsants/

Concurrent use of phenacemide with dione anticonvulsants may result in additive toxicity. /Dione anticonvulsants/

Dione anticonvulsants such as paramethadione reduce T-type calcium currents in thalamic neurons (including thalamic relay neurons). This inhibits corticothalamic transmission and raises the threshold for repetitive activity in the thalamus. This results in a dampening of the abnormal thalamocortical rhythmicity proposed to underlie the 3-Hz spike-and-wave discharge seen on electroencephalogram (EEG) during absence seizures.

Symptoms of overdose include clumsiness or unsteadiness, coma, severe dizziness, severe drowsiness, severe nausea, and problems with vision. May cause a potentially dangerous rash that may develop into Stevens Johnson syndrome, an extremely rare but potentially fatal skin disease.

SEDATION MAY OCCUR WITH HIGH DOSES. UNCOMFORTABLE VISUAL ALTERATIONS, PARTICULARLY UNPLEASANT GLARE WHEN EMERGING INTO SUNLIGHT OR WELL-LIT ROOM... EDEMA & SEVERE PROTEIN-LOSING NEPHROPATHY MAY OCCUR... NEUTROPENIA OCCURS IN ABOUT 20% OF RECIPIENTS & OCCASIONALLY PANCYTOPENIA & FATAL APLASTIC ANEMIA HAVE BEEN REPORTED.

OTHER ADVERSE EFFECTS INCL HEPATITIS, SKIN REACTIONS (GENERALIZED ERYTHEMA, MACULOPAPULAR ERUPTIONS & EXFOLIATIVE DERMATITIS) &, RARELY, MILD GI DISTURBANCES.

Acute effects of overdose include ataxia (clumsiness or unsteadiness); coma - following massive overdose; severe dizziness; severe drowsiness; severe nausea; and visual disturbances.

The neuroactive drugs taken by pregnant women have two principal side effects: a teratogenic effect and a postnatal withdrawal effect. /The following characteristic syndromes are noted/: hydantoin-barbiturate syndrome, the trimethadione-paramethadione syndrome.

Treatment of overdose: To decrease absorption - immediate evacuation of stomach by induction of emesis, lavage, or both is recommended. To enhance elimination - alkalinization of urine is reported to enhance elimination of active metabolites. Monitoring - frequent monitoring of vital signs and close patient observation are required. Following recovery, a complete blood count and a careful evaluation of hepatic and renal function should be done. Supportive care - general supportive care is necessary in dione anticonvulsant overdose treatment. Patients in whom intentional overdose is confirmed or suspected should be referred for psychiatric consultation. /Dione anticonvulsants/

Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).

MEDICATION (VET)

MEDICATION

Therap Cat: Anticonvulsant.

Used for the control of absence (petit mal) seizures that are refractory to treatment with other medications.

SPIELMAN, US PATENT 2,575,693 (1951 TO ABBOTT).

ETHYL ALPHA-HYDROXY-ALPHA-METHYLBUTYRATE & UREA...REFLUXED FOR 24 HR IN PRESENCE OF SODIUM METHOXIDE, RESULTING IN CONDENSATION CYCLIZATION WITH FORMATION OF SODIUM DERIV OF 5-ETHYL-5-METHYL-2,4-OXAZOLIDINEDIONE. AFTER DISTILLING OFF ALC, DIMETHYL SULFATE...ADDED TO EFFECT DESIRED N-METHYLATION.